4615 Background: International studies have described the clinical characteristics and outcomes of patients with HCC. However, patient demographics, tumor characteristics, extent of liver disease, risk factors, treatment and outcome are less well established in the United States (US) where HCC remains rare. Methods: We identified 328 patients presenting to Beth Israel Deaconess Medical Center with a new diagnosis of HCC from 1998–2005. Characteristics including risk factors, underlying liver disease, tumor morphology and treatment were entered into a retrospective database. Child-Pugh grade and Cancer of the Liver Italian Program (CLIP) score were determined. Survival analysis was performed and data compared to our previously published HCC cohort from 1985–1995. Results: Patient characteristics were: Median age: 62; Male: 81%; Alcohol use (EtOH): 44%; Hepatitis C (HCV): 38%; Hepatitis B (HBV): 21%; No Risk Factor: 15%. EtOH was more common in HCV (57%) than in HBV (18%) patients. Treatment modality was: liver transplantation (LT) 14.4%, surgical resection 7.8%, chemoembolization or radiofrequency ablation (CE/RFA) 36%, chemotherapy 22%, no treatment 16%. Median overall survival was 13.5 months. Significantly better median survival was associated with Child-Pugh grade A (20.3 mos.), uninodular tumor in <50% of liver (34.3 mos.), absence of portal vein thrombosis (19.2 mos.), CLIP score of 0 (42.5 mos.), background of HBV (32.9 mos.) and No EtOH (16.2 mos.). Treatment correlated with survival: LT, resection, or CE/RFA showed significantly better survival than chemotherapy or no treatment. In comparison to the 1985–95 cohort, median survival improved from 10 to 13.5 months. The 1998–05 cohort had more HBV/HCV (57% versus 20%), more favorable tumor characteristics, less severe liver disease, and more LT (14.4% versus 2.8%). Conclusions: In this single US institution, survival of HCC patients improved by 35% over two decades. Our results are consistent with nationwide trends of increased prevalence of viral infection, screening to find earlier disease, and more widespread use of aggressive treatments. Changing patterns of approaching the cirrhotic patient with HCC may be leading to slightly better results. No significant financial relationships to disclose.